Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Raffaella Parente
  • Barbara Bottazzi
  • Alberto Mantovani
  • Antonio InforzatoEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101746


Historical Background

Innate immunity sets in evolution as the earliest line of defense against pathogens. Endowed with pivotal roles in activation and orientation of the adaptive immune response, this ancient system is deeply involved in a number of physiological and pathological processes, ranging from tissue homeostasis to cancer growth and development. Innate immunity comprises a cellular and humoral arm, the latter encompassing soluble pattern recognition molecules (PRMs) that recognize pathogen- and danger-associated molecular patterns (PAMPs and DAMPs, respectively) and initiate the immune response in coordination with the cellular arm (Bottazzi et al. 2010). Pentraxins are a phylogenetically conserved superfamily of soluble PRMs that, based on primary structure, is divided into two subfamilies: short and long pentraxins. Prototypes of the short pentraxins, C-reactive protein (CRP), and serum amyloid P (SAP)...

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  1. Bonavita E, Gentile S, Rubino M, Maina V, Papait R, Kunderfranco P, et al. PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer. Cell. 2015;160(4):700–14.  https://doi.org/10.1016/j.cell.2015.01.004.CrossRefPubMedGoogle Scholar
  2. Bottazzi B, Doni A, Garlanda C, Mantovani A. An integrated view of humoral innate immunity: pentraxins as a paradigm. Annu Rev Immunol. 2010;28:157–83.  https://doi.org/10.1146/annurev-immunol-030409-101305.CrossRefPubMedGoogle Scholar
  3. Bozza S, Bistoni F, Gaziano R, Pitzurra L, Zelante T, Bonifazi P, et al. Pentraxin 3 protects from MCMV infection and reactivation through TLR sensing pathways leading to IRF3 activation. Blood. 2006;108(10):3387–96.  https://doi.org/10.1182/blood-2006-03-009266.CrossRefPubMedGoogle Scholar
  4. Deban L, Russo RC, Sironi M, Moalli F, Scanziani M, Zambelli V, et al. Regulation of leukocyte recruitment by the long pentraxin PTX3. Nat Immunol. 2010;11(4):328–34.  https://doi.org/10.1038/ni.1854.CrossRefPubMedGoogle Scholar
  5. Doni A, Garlanda C, Bottazzi B, Meri S, Garred P, Mantovani A. Interactions of the humoral pattern recognition molecule PTX3 with the complement system. Immunobiology. 2012;217(11):1122–8.  https://doi.org/10.1016/j.imbio.2012.07.004.CrossRefPubMedGoogle Scholar
  6. Doni A, Musso T, Morone D, Bastone A, Zambelli V, Sironi M, et al. An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode. J Exp Med. 2015;212(6):905–25.  https://doi.org/10.1084/jem.20141268.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Foo SS, Chen W, Taylor A, Sheng KC, Yu X, Teng TS, et al. Role of pentraxin 3 in shaping arthritogenic alphaviral disease: from enhanced viral replication to immunomodulation. PLoS Pathog. 2015;11(2):e1004649.  https://doi.org/10.1371/journal.ppat.1004649.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Garlanda C, Hirsch E, Bozza S, Salustri A, De Acetis M, Nota R, et al. Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature. 2002;420(6912):182–6.  https://doi.org/10.1038/nature01195.CrossRefPubMedGoogle Scholar
  9. Garlanda C, Jaillon S, Doni A, Bottazzi B, Mantovani A. PTX3, a humoral pattern recognition molecule at the interface between microbe and matrix recognition. Curr Opin Immunol. 2016;38:39–44.  https://doi.org/10.1016/j.coi.2015.11.002.CrossRefPubMedGoogle Scholar
  10. Infante M, Allavena P, Garlanda C, Nebuloni M, Morenghi E, Rahal D, et al. Prognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients. Int J Cancer. 2016;138(4):983–91.  https://doi.org/10.1002/ijc.29822.CrossRefPubMedGoogle Scholar
  11. Inforzato A, Baldock C, Jowitt TA, Holmes DF, Lindstedt R, Marcellini M, et al. The angiogenic inhibitor long pentraxin PTX3 forms an asymmetric octamer with two binding sites for FGF2. J Biol Chem. 2010;285(23):17681–92.  https://doi.org/10.1074/jbc.M109.085639.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Inforzato A, Jaillon S, Moalli F, Barbati E, Bonavita E, Bottazzi B, et al. The long pentraxin PTX3 at the crossroads between innate immunity and tissue remodelling. Tissue Antigens. 2011;77(4):271–82.  https://doi.org/10.1111/j.1399-0039.2011.01645.x.CrossRefPubMedGoogle Scholar
  13. Inforzato A, Reading PC, Barbati E, Bottazzi B, Garlanda C, Mantovani A. The “sweet” side of a long pentraxin: how glycosylation affects PTX3 functions in innate immunity and inflammation. Front Immunol. 2013;3:407.  https://doi.org/10.3389/fimmu.2012.00407.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Jaillon S, Peri G, Delneste Y, Frémaux I, Doni A, Moalli F, et al. The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localizes in extracellular traps. J Exp Med. 2007;204(4):793–804.  https://doi.org/10.1084/jem.20061301.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Jeannin P, Bottazzi B, Sironi M, Doni A, Rusnati M, Presta M, et al. Complexity and complementarity of outer membrane protein A recognition by cellular and humoral innate immunity receptors. Immunity. 2005;22(5):551–60.  https://doi.org/10.1016/j.immuni.2005.03.008.CrossRefPubMedGoogle Scholar
  16. Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–44.  https://doi.org/10.1038/nature07205.CrossRefPubMedCentralPubMedGoogle Scholar
  17. Moalli F, Doni A, Deban L, Zelante T, Zagarella S, Bottazzi B, et al. Role of complement and Fc{gamma} receptors in the protective activity of the long pentraxin PTX3 against Aspergillus fumigatus. Blood. 2010;116(24):5170–80.  https://doi.org/10.1182/blood-2009-12-258376.CrossRefPubMedCentralPubMedGoogle Scholar
  18. Reading PC, Bozza S, Gilbertson B, Tate M, Moretti S, Job ER, et al. Antiviral activity of the long chain pentraxin PTX3 against influenza viruses. J Immunol. 2008;180(5):3391–8.  https://doi.org/10.4049/jimmunol.180.5.3391.CrossRefPubMedCentralPubMedGoogle Scholar
  19. Ronca R, Giacomini A, Di Salle E, Coltrini D, Pagano K, Ragona L, et al. Long-pentraxin 3 derivative as a small-molecule FGF trap for cancer therapy. Cancer Cell. 2015;28(2):225–39.  https://doi.org/10.1016/j.ccell.2015.07.002.CrossRefPubMedCentralPubMedGoogle Scholar
  20. Salio M, Chimenti S, De Angelis N, Molla F, Maina V, Nebuloni M, et al. Cardioprotective function of the long pentraxin PTX3 in acute myocardial infarction. Circulation. 2008;117(8):1055–64.  https://doi.org/10.1161/CIRCULATIONAHA.107.749234.CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Raffaella Parente
    • 1
  • Barbara Bottazzi
    • 1
  • Alberto Mantovani
    • 1
    • 2
  • Antonio Inforzato
    • 1
    • 3
    Email author
  1. 1.Department of Inflammation and ImmunologyHumanitas Clinical and Research CenterRozzanoItaly
  2. 2.Humanitas UniversityRozzanoItaly
  3. 3.Department of Medical Biotechnologies and Translational MedicineUniversity of MilanMilanItaly